1. Field of the Invention
The present invention relates to compositions and methods of treatment for sexual dysfunctions, and more particularly, to the treatment of premature ejaculation in male subjects by administration of delta receptor agonist compound(s), optionally in combination with other agents.
2. Description of the Related Art
Premature ejaculation is one of the most common male sexual dysfunctions, estimated to affect up to 40% of men, irrespective of age. Premature ejaculation is defined as a persistent or recurrent ejaculation with minimal sexual stimulation before, on or shortly after penetration. Although premature ejaculation is common, there is some disagreement on its precise cause and treatment.
The reasons for premature ejaculation are generally thought to include a malfunction of the repressor center due to the fatigue of nervous transmission, hypersensitivity of a specific site due to genital disorders, hormonal disorders, physical problems and the like. It is believed that the premature ejaculation is generally caused by a complex interaction of the above-mentioned reasons or by a loss of cooperation among the related sexual nerve centers.
Premature ejaculation has been treated with psychotherapy and drug therapy. Psychotherapy requires sexual training for a long period of time, which involves discussions and cooperation with a physician and the patient and his partner. However, since psychotherapy necessitates a long period of time for the doctor, patient and partner to work together in order to be effective, its success rate is low. That is, changes in living style, external stress, etc., undermine its success such that the problem is never solved or it reoccurs. Therefore, drug therapy is now more widely used since time restrictions are not as great.
Methods for treating premature ejaculation by systemic administration of several different antidepressant compounds have been described in U.S. Pat. Nos. 5,151,448 and 5,276,042. However, these drugs may not be effective for all patients, and the side effects of these drugs can halt treatment or impair patient compliance. Disease states or adverse interactions with other drugs may contraindicate the use of these compounds or require lower dosages that may not be effective to delay the onset of ejaculation. Additionally, the stigma of mental illness associated with antidepressant therapy can discourage patients from beginning or continuing such treatments.
Administration of the antidepressant fluoxetine has been claimed to treat premature ejaculation (U.S. Pat. No. 5,151,448). However, the administration of fluoxetine has many undesired aspects. Patients with hepatic or renal impairments may not be able to use fluoxetine due to its metabolism in the liver and excretion via the kidney. Systemic events during fluoxetine treatment involving the lungs, kidneys or liver have occurred, and death has occurred from overdoses. In addition, side effects of oral fluoxetine administration include hair loss, nausea, vomiting, dyspepsia, diarrhea, anorexia, anxiety, nervousness, insomnia, drowsiness, fatigue, headache, tremors, dizziness, convulsions, sweating and skin rashes. Fluoxetine interacts with a range of drugs, often by impairing their metabolism by the liver.
U.S. Pat. No. 5,276,042 describes the administration of paroxetine for the treatment of premature ejaculation. Paroxetine is predominantly excreted in the urine, and decreased doses are recommended in patients with hepatic and renal impairments. Paroxetine cannot be given to patients undergoing treatment with a monoamine oxidase inhibitor. Side effects from oral administration of paroxetine include hyponatremia, asthenia, sweating, nausea, decreased appetite, oropharynx disorder, somnolence, dizziness, insomnia, tremors, anxiety, impaired micturition, weakness and paresthesia.
Other therapies include the application of local anesthetics for blunting the sensitivity of the sexual peripheral nerve. However, local anesthetics, such as lidocaine ointment or spray, may induce vasoconstriction, which may lead to transient erectile failure, and can be transferred to sexual partners thereby decreasing their sensitivity and pleasure as well.
Thus, present day drug therapy cannot successfully solve the problems associated with premature ejaculation. Accordingly there is a need for a method of treating premature ejaculation that requires no specialized psychological therapy, can be used conveniently and without embarrassment, and does not involve the problems associated with prior therapeutic methods.